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Proinflammatory effect of trivalent arsenical species in a co-culture of Caco-2 cells and peripheral blood mononuclear cells

  • Inorganic Compounds
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Abstract

Chronic exposure to inorganic arsenic (As) is associated with type 2 diabetes, cardiovascular diseases and cancer. Ingested inorganic As is transformed within the gastrointestinal tract and can give rise to more toxic species such as monomethylarsonous acid [MMA(III)] and dimethylarsinous acid [DMA(III)]. Thus, the intestinal epithelium comes into contact with toxic arsenical species, and the effects of such exposure upon epithelial function are not clear. The present study has evaluated the effect of 1 µM arsenite [As(III)], 0.1 µM MMA(III) and 1 µM DMA(III) upon the release of cytokines [interleukin-6 (IL6), IL8, tumor necrosis factor alpha (TNFα)], using a compartmentalized co-culture model with differentiated Caco-2 cells in the apical compartment and peripheral blood mononuclear cells in the basolateral compartment. In addition, the combined effect of arsenical species and lipopolysaccharide (LPS), both added into the apical compartment, has been analyzed. The results indicate that exposure to the arsenical forms induces a proinflammatory response. An increase in cytokine secretion into the basolateral compartment was observed, particularly as regards TNFα (up to 1,600 %). The cytokine levels on the apical side also increased, though to a lesser extent. As/LPS co-exposure significantly affected the proinflammatory response as compared to treatment with As alone. Treatment with DMA(III) and As/LPS co-exposure increased the permeability of the intestinal monolayer. In addition, As/LPS treatments enhanced As(III) and MMA(III) transport through the intestinal monolayer.

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Acknowledgments

This work was supported by the Spanish Ministry of Science and Innovation (AGL2009-10100) and the Ministry of Economy and Competitiveness (AGL2012-33461), for which the authors are deeply indebted. Marta Calatayud received a Personnel Training Grant from the Spanish Ministry of Science and Education to carry out this study. The authors also thank Ivonne Eneme Watson for help provided in carrying out this study.

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  1. Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC), Avda. Agustín Escardino 7, 46980, Paterna, Valencia, Spain

    Marta Calatayud, José V. Gimeno-Alcañiz, Vicenta Devesa & Dinoraz Vélez

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  1. Marta Calatayud
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  2. José V. Gimeno-Alcañiz
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  3. Vicenta Devesa
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  4. Dinoraz Vélez
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Correspondence to Dinoraz Vélez.

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Calatayud, M., Gimeno-Alcañiz, J.V., Devesa, V. et al. Proinflammatory effect of trivalent arsenical species in a co-culture of Caco-2 cells and peripheral blood mononuclear cells. Arch Toxicol 89, 555–564 (2015). https://doi.org/10.1007/s00204-014-1271-1

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